TY - JOUR
T1 - Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve
AU - Perlson, Eran
AU - Hanz, Shlomit
AU - Ben-Yaakov, Keren
AU - Segal-Ruder, Yael
AU - Seger, Rony
AU - Fainzilber, Mike
N1 - Funding Information:
This work was supported by grants from the Minerva Foundation, the Pasteur-Weizmann Foundation, and the Christopher Reeve Paralysis Foundation. M.F. is the incumbent of the Daniel Koshland Sr. Career Development Chair at the Weizmann Institute. We are very grateful to Emma Colucci-Guyon for the generous gift of vimentin −/− mice, and to Daniel Gonzalez-Dunia for invaluable assistance in transferring the mice. We thank Michael Elbaum and Dafna Frenkiel for electron microscopy of vimentin filaments; Vladimir Kiss for assistance with confocal microscopy; and Steve Adam, Elior Peles, Ziv Reich, and Karsten Weis for kind gifts of antibodies and reagents. Finally, we very much appreciate the constructive criticisms of Ari Elson, Carlos Ibanez, and the reviewers.
PY - 2005/3/3
Y1 - 2005/3/3
N2 - How are phosphorylated kinases transported over long intracellular distances, such as in the case of axon to cell body signaling after nerve injury? Here, we show that the MAP kinases Erk1 and Erk2 are phosphorylated in sciatic nerve axoplasm upon nerve injury, concomitantly with the production of soluble forms of the intermediate filament vimentin by local translation and calpain cleavage in axoplasm. Vimentin binds phosphorylated Erks (pErk), thus linking pErk to the dynein retrograde motor via direct binding of vimentin to importin β. Injury-induced Elk1 activation and neuronal regeneration are inhibited or delayed in dorsal root ganglion neurons from vimentin null mice, and in rats treated with a MEK inhibitor or with a peptide that prevents pErk-vimentin binding. Thus, soluble vimentin enables spatial translocation of pErk by importins and dynein in lesioned nerve.
AB - How are phosphorylated kinases transported over long intracellular distances, such as in the case of axon to cell body signaling after nerve injury? Here, we show that the MAP kinases Erk1 and Erk2 are phosphorylated in sciatic nerve axoplasm upon nerve injury, concomitantly with the production of soluble forms of the intermediate filament vimentin by local translation and calpain cleavage in axoplasm. Vimentin binds phosphorylated Erks (pErk), thus linking pErk to the dynein retrograde motor via direct binding of vimentin to importin β. Injury-induced Elk1 activation and neuronal regeneration are inhibited or delayed in dorsal root ganglion neurons from vimentin null mice, and in rats treated with a MEK inhibitor or with a peptide that prevents pErk-vimentin binding. Thus, soluble vimentin enables spatial translocation of pErk by importins and dynein in lesioned nerve.
UR - http://www.scopus.com/inward/record.url?scp=14644404885&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2005.01.023
DO - 10.1016/j.neuron.2005.01.023
M3 - מאמר
AN - SCOPUS:14644404885
VL - 45
SP - 715
EP - 726
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 5
ER -